The present invention relates to a method for preparing a highly purified N-long chain acyl neutral amino acid, which is useful for manufacture of detergents and the like, in a simple and convenient manner and in a high yield.
Amine salts or alkali metal salts of N-long chain acyl neutral amino acids have superior surface activating and bacteriostatic action and also have low irritancy. Accordingly, they are useful for manufacture of detergents with a mild action to the skin. Since these amine salts or alkali metal salts of N-long chain acyl neutral amino acids are often utilized as a detergent component of quasi drugs and cosmetics, they are required to have as little smell and impurities as possible. In particular, impurities may affect functions or feelings inherently achieved by the compounds. As a method for preparing the N-long chain acylamino acid, in general, a method is known which comprises the steps of condensing an amino acid and a fatty acid halide under an alkali condition by the Schotten-Baumann reaction, and then isolating the product as an acylamino acid by using an acid.
As for preparation of acyl neutral amino acids, it is known that the reaction advances even though water alone is used as a solvent, as disclosed in Japanese Patent Unexamined Publication (Kokai) Nos. 7-157795 and 5-70418. However, when water alone is used as a solvent, a purity of the acylated compound does not exceed a level of little more than about 90%, and it is difficult to obtain the compound with a high purity. Further, the reaction system suffers from extremely high viscosity of a reaction mixture, which results in insufficient stirring at a high concentration and a further deterioration of a purity. Therefore, the reaction is inevitably carried out at a low concentration that allows stirring, and for this reason, the reaction is economically disadvantageous. As an economical method performable at a high concentration, a method is disclosed in the aforementioned patent document which involves an increase of a reaction temperature with a progress of the acylation. However, also in this method, viscosity of the reaction mixture is still high to load equipments, and further, if uniform starring is insufficient, a deterioration of a purity may sometimes arise.
As a method for obtaining an acylamino acid with a high purity, the water/acetone mixed-solvent method is generally used for acidic amino acids. Although this system successfully gives a target substance with a high purity, no tendency of viscosity reduction due to the presence of the organic solvent is observed. Japanese Patent Publication (Kokoku) No. 51-38681 discloses a method of using a primary alcohol as a reaction solvent for condensation of an amino acid and a fatty acid halide in the presence of an alkali. However, in this reaction, low concentrations of the reaction species are applied to perform the reaction in a region where sufficient stirring is possible with water alone, and therefore, the aforementioned patent document neither suggests nor teaches a possibility of viscosity reduction by use of a primary alcohol. Further, although this method enables preparation of the target substance with high purity, an ester may possibly be produced by the reaction of the primary alcohol and fatty acid chloride and heating under an acidic condition after the reaction, which arises problems of degradation of properties such as foaming property and generation of smell of the produced ester.
As a method for purifying an N-long chain acyl neutral amino acid, a method is disclosed in Japanese Patent Unexamined Publication No. 5-70418 which comprises isolation of an N-long chain acylamino acid as crystals and washing said crystals. However, this method requires an apparatus for separating the crystals, and the step of washing with water needs undesirably prolonged period of time when certain kinds of acylamino acids have poor crystallizing properties. Accordingly, the method is not desirable from viewpoints of facilities and efficiency. Further, Japanese Patent Unexamined Publication No. 7-157795 discloses a method of desalting an N-long chain acylamino acid in water by adding a fatty acid or the like so as to facilitate separation of an organic layer and an aqueous layer. However, this method has a problem in that a purity of the N-long chain acylamino acid is degraded.
An object of the present invention is to provide a method for obtaining a highly purified N-long chain acyl neutral amino acid efficiently and in a high yield. Further, another object of the present invention is to provide a method for preparing an N-long chain acyl neutral amino acid, which enables easy isolation of a highly purified N-long chain acyl neutral amino acid in a simple and convenient manner.
The inventors of the present invention conducted various researches to achieve the aforementioned objects. As a result, they found that, for preparation of an N-long chain acyl neutral amino acid by a reaction of a neutral amino acid and a fatty acid halide, when a mixture of water and one or more kinds of hydrophilic organic solvents selected from the group consisting of acetone, acetonitrile, a secondary alcohol having 3 or 4 carbon atoms, and a tertiary alcohol having 4 carbon atoms is used as a solvent, viscosity of the reaction mixture was markedly reduced compared with a process where the reaction was performed by using water as a sole solvent, and thus the reaction yield was be remarkably improved. They further found that, when the resulting reaction mixture was heated under an acidic condition, rapid separation of an organic layer and an aqueous layer occurred, thereby desalting was more efficiently conductible than the system utilizing water as a sole solvent. The present invention was achieved on the basis of these findings.
The present invention thus provides a method for producing an N-long chain acyl neutral amino acid by a reaction of a neutral amino acid and a saturated or unsaturated fatty acid halide having 8 to 22 carbon atoms, wherein the reaction is performed in a mixture of water and one or more kinds of hydrophilic organic solvents selected from the group consisting of acetone, acetonitrile, a secondary alcohol having 3 or 4 carbon atoms, and a tertiary alcohol having 4 carbon atoms in the presence of a base.
According to preferred embodiments of the present invention, provided are the aforementioned method, wherein the hydrophilic organic solvent consists of one or more kinds of hydrophilic organic solvents selected from the group consisting of isopropanol, sec-butanol, and tert-butanol; the aforementioned method, wherein the hydrophilic solvent consists of tert-butanol; and the aforementioned method, wherein the neutral amino acid is glycine, xcex3-aminobutyric acid, alanine, valine, leucine, isoleucine, serine, or threonine.
The present invention further provides the aforementioned method, which further comprises the steps of warming a reaction mixture adjusted to pH 1 to 6 to a temperature of 35xc2x0 C. or higher for separation of an organic layer and an aqueous layer, and recovering the N-long chain acyl neutral amino acid from the organic layer. More specifically, the present invention provides a method for preparing an N-long chain acyl neutral amino acid by a reaction of a neutral amino acid and a saturated or unsaturated fatty acid halide having 8 to 22 carbon atoms, which comprises the following steps of (1) performing the reaction in a mixture of water and one or more kinds of hydrophilic organic solvents selected from the group consisting of acetone, acetonitrile, a secondary alcohol having 3 or 4 carbon atoms, and a tertiary alcohol having 4 carbon atoms in the presence of a base, and (2) warming a reaction mixture adjusted to pH 1 to 6 to a temperature of 35xc2x0 C. or higher for separation of an organic layer and an aqueous layer, and recovering the N-long chain acyl neutral amino acid from the organic layer.
According to the preparation method of the present invention, highly purified N-long chain acyl neutral amino acids, which are useful for manufacture of detergents and the like, can be prepared in a high yield in a simple and convenient manner.